After discovery of mammalian collagenases it has become essential to discover more about how production of these enzymes is modulated in health and disease, and how synthesis and release of enzymes are controlled. In the coming year we will purify the inhibitor of collagenase found in human tendon strip culture medium, compare this inhibitor with circulating beta anti-collagenase, and use the inhibitor to purify collagenase. We will continue to investigate the effect of phorbal myristate acetate on synovial fibroblast cultures: large amounts of collagenase are produced. The effect is not caused by prostaglandins but is inhibited by gamma-amanatin which inhibits formation of messenger RNA. This model is an ideal one for exploring the exact nature of the common denominator in cells which responds to stimulation of exogenous agents to induce collagenase.